Skip to content
2000
image of Advances in Alzheimer's Disease Biomarkers

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual onset and complex pathological mechanisms. Clinically, it presents with progressive cognitive decline and behavioral impairments, making it one of the most common causes of dementia. The intricacies of its pathogenesis are not fully understood, and current treatment options are limited, with diagnosis typically occurring at intermediate to advanced stages. The development of new biomarkers offers a crucial avenue for the early diagnosis of AD and improving patient outcomes. Several biomarkers with high specificity have been identified. This article reviews biomarkers related to tau protein, β-amyloid, and blood cells to deepen our understanding of AD and emphasize the advantages and disadvantages of various biomarkers in order to explore further and mine new biomarkers for AD diagnosis.

Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050366767241223050957
2024-12-26
2025-01-18
Loading full text...

Full text loading...

References

  1. Winblad B. Amouyel P. Andrieu S. Ballard C. Brayne C. Brodaty H. Cedazo-Minguez A. Dubois B. Edvardsson D. Feldman H. Fratiglioni L. Frisoni G.B. Gauthier S. Georges J. Graff C. Iqbal K. Jessen F. Johansson G. Jönsson L. Kivipelto M. Knapp M. Mangialasche F. Melis R. Nordberg A. Rikkert M.O. Qiu C. Sakmar T.P. Scheltens P. Schneider L.S. Sperling R. Tjernberg L.O. Waldemar G. Wimo A. Zetterberg H. Defeating Alzheimer’s disease and other dementias: a priority for European science and society. Lancet Neurol. 2016 15 5 455 532 10.1016/S1474‑4422(16)00062‑4 26987701
    [Google Scholar]
  2. Chen Z.Y. Zhang Y. Animal models of Alzheimer’s disease: Applications, evaluation, and perspectives. Zool. Res. 2022 43 6 1026 1040 10.24272/j.issn.2095‑8137.2022.289 36317468
    [Google Scholar]
  3. Kinsella G.J. Mullaly E. Rand E. Ong B. Burton C. Price S. Phillips M. Storey E. Early intervention for mild cognitive impairment: A randomised controlled trial. J. Neurol. Neurosurg. Psychiatry 2009 80 7 730 736 10.1136/jnnp.2008.148346 19332424
    [Google Scholar]
  4. Gillis C. Mirzaei F. Potashman M. Ikram M.A. Maserejian N. The incidence of mild cognitive impairment: A systematic review and data synthesis. Alzheimers Dement. (Amst.) 2019 11 1 248 256 10.1016/j.dadm.2019.01.004 30911599
    [Google Scholar]
  5. Monteiro A.R. Barbosa D.J. Remião F. Silva R. Alzheimer’s disease: Insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs. Biochem. Pharmacol. 2023 211 115522 10.1016/j.bcp.2023.115522 36996971
    [Google Scholar]
  6. Mantzavinos V. Alexiou A. Biomarkers for alzheimer’s disease diagnosis. Curr. Alzheimer Res. 2017 14 11 1149 1154 28164766
    [Google Scholar]
  7. Magalingam K.B. Radhakrishnan A. Ping N.S. Haleagrahara N. Current concepts of neurodegenerative mechanisms in alzheimer’s disease. BioMed Res. Int. 2018 2018 1 12 10.1155/2018/3740461 29707568
    [Google Scholar]
  8. Imbimbo B.P. Watling M. Investigational BACE inhibitors for the treatment of Alzheimer’s disease. Expert Opin. Investig. Drugs 2019 28 11 967 975 10.1080/13543784.2019.1683160 31661331
    [Google Scholar]
  9. Wang X. Sun G. Feng T. Zhang J. Huang X. Wang T. Xie Z. Chu X. Yang J. Wang H. Chang S. Gong Y. Ruan L. Zhang G. Yan S. Lian W. Du C. Yang D. Zhang Q. Lin F. Liu J. Zhang H. Ge C. Xiao S. Ding J. Geng M. Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression. Cell Res. 2019 29 10 787 803 10.1038/s41422‑019‑0216‑x 31488882
    [Google Scholar]
  10. Wang H.Y. Pei Z. Lee K.C. Lopez-Brignoni E. Nikolov B. Crowley C.A. Marsman M.R. Barbier R. Friedmann N. Burns L.H. PTI-125 reduces biomarkers of alzheimer’s disease in patients. J. Prev. Alzheimers Dis. 2020 7 4 256 264 32920628
    [Google Scholar]
  11. Savelieff M.G. Nam G. Kang J. Lee H.J. Lee M. Lim M.H. Development of multifunctional molecules as potential therapeutic candidates for alzheimer’s disease, parkinson’s disease, and amyotrophic lateral sclerosis in the last decade. Chem. Rev. 2019 119 2 1221 1322 10.1021/acs.chemrev.8b00138 30095897
    [Google Scholar]
  12. Ismaili L. Refouvelet B. Benchekroun M. Brogi S. Brindisi M. Gemma S. Campiani G. Filipic S. Agbaba D. Esteban G. Unzeta M. Nikolic K. Butini S. Marco-Contelles J. Multitarget compounds bearing tacrine- and donepezil-like structural and functional motifs for the potential treatment of Alzheimer’s disease. Prog. Neurobiol. 2017 151 4 34 10.1016/j.pneurobio.2015.12.003 26797191
    [Google Scholar]
  13. Rao C.V. Asch A.S. Carr D.J.J. Yamada H.Y. “Amyloid‐beta accumulation cycle” as a prevention and/or therapy target for Alzheimer’s disease. Aging Cell 2020 19 3 e13109 10.1111/acel.13109 31981470
    [Google Scholar]
  14. Sperling R.A. Jack C.R. Jr Aisen P.S. Testing the right target and right drug at the right stage. Sci. Transl. Med. 2011 3 111 111cm33 10.1126/scitranslmed.3002609 22133718
    [Google Scholar]
  15. Blennow K. Biomarkers in Alzheimer’s disease drug development. Nat. Med. 2010 16 11 1218 1222 10.1038/nm.2221 21052077
    [Google Scholar]
  16. Beach T.G. Monsell S.E. Phillips L.E. Kukull W. Accuracy of the clinical diagnosis of alzheimer disease at national institute on aging alzheimer disease centers, 2005–2010. J. Neuropathol. Exp. Neurol. 2012 71 4 266 273 10.1097/NEN.0b013e31824b211b 22437338
    [Google Scholar]
  17. Wegmann S. Biernat J. Mandelkow E. A current view on tau protein phosphorylation in alzheimer’s disease. Curr. Opin. Neurobiol. 2021 69 131 138 10.1016/j.conb.2021.03.003 33892381
    [Google Scholar]
  18. Karikari T.K. Ashton N.J. Brinkmalm G. Brum W.S. Benedet A.L. Montoliu-Gaya L. Lantero-Rodriguez J. Pascoal T.A. Suárez-Calvet M. Rosa-Neto P. Blennow K. Zetterberg H. Blood phospho-tau in alzheimer disease: analysis, interpretation, and clinical utility. Nat. Rev. Neurol. 2022 18 7 400 418 10.1038/s41582‑022‑00665‑2 35585226
    [Google Scholar]
  19. Waheed Z. Choudhary J. Jatala F.H. Fatimah Noor A. Zerr I. Zafar S. The role of tau proteoforms in health and disease. Mol. Neurobiol. 2023 60 9 5155 5166 10.1007/s12035‑023‑03387‑8 37266762
    [Google Scholar]
  20. Palmqvist S. Tideman P. Cullen N. Zetterberg H. Blennow K. Dage J.L. Stomrud E. Janelidze S. Mattsson-Carlgren N. Hansson O. Prediction of future Alzheimer’s disease dementia using plasma phospho-tau combined with other accessible measures. Nat. Med. 2021 27 6 1034 1042 10.1038/s41591‑021‑01348‑z 34031605
    [Google Scholar]
  21. Campese N. Palermo G. Del Gamba C. Beatino M.F. Galgani A. Belli E. Del Prete E. Della Vecchia A. Vergallo A. Siciliano G. Ceravolo R. Hampel H. Baldacci F. Progress regarding the context-of-use of tau as biomarker of Alzheimer’s disease and other neurodegenerative diseases. Expert Rev. Proteomics 2021 18 1 27 48 10.1080/14789450.2021.1886929 33545008
    [Google Scholar]
  22. Papaliagkas V. Kalinderi K. Vareltzis P. Moraitou D. Papamitsou T. Chatzidimitriou M. CSF biomarkers in the early diagnosis of mild cognitive impairment and alzheimer’s disease. Int. J. Mol. Sci. 2023 24 10 8976 10.3390/ijms24108976 37240322
    [Google Scholar]
  23. Blennow K. Cerebrospinal fluid protein biomarkers for Alzheimer’s disease. NeuroRx 2004 1 2 213 225 10.1602/neurorx.1.2.213 15717022
    [Google Scholar]
  24. Schönknecht P. Pantel J. Kaiser E. Thomann P. Schröder J. Increased tau protein differentiates mild cognitive impairment from geriatric depression and predicts conversion to dementia. Neurosci. Lett. 2007 416 1 39 42 10.1016/j.neulet.2007.01.070 17331644
    [Google Scholar]
  25. Meredith J.E. Jr Sankaranarayanan S. Guss V. Lanzetti A.J. Berisha F. Neely R.J. Slemmon J.R. Portelius E. Zetterberg H. Blennow K. Soares H. Ahlijanian M. Albright C.F. Characterization of novel CSF Tau and ptau biomarkers for Alzheimer’s disease. PLoS One 2013 8 10 e76523 10.1371/journal.pone.0076523 24116116
    [Google Scholar]
  26. Fiandaca M.S. Kapogiannis D. Mapstone M. Boxer A. Eitan E. Schwartz J.B. Abner E.L. Petersen R.C. Federoff H.J. Miller B.L. Goetzl E.J. Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case‐control study. Alzheimers Dement. 2015 11 6 600 7.e1 10.1016/j.jalz.2014.06.008 25130657
    [Google Scholar]
  27. Blennow K. A Review of Fluid Biomarkers for Alzheimer’s Disease: Moving from CSF to Blood. Neurol. Ther. 2017 6 Suppl 1 15 24 10.1007/s40120‑017‑0073‑9 28733960
    [Google Scholar]
  28. Marksteiner J. Defrancesco M. Humpel C. Saliva tau and phospho-tau-181 measured by Lumipulse in patients with Alzheimer’s disease. Front. Aging Neurosci. 2022 14 1014305 10.3389/fnagi.2022.1014305 36247998
    [Google Scholar]
  29. Gonzalez-Ortiz F. Karikari T.K. Bentivenga G.M. Baiardi S. Mammana A. Turton M. Kac P.R. Mastrangelo A. Harrison P. Capellari S. Zetterberg H. Blennow K. Parchi P. Levels of plasma brain‐derived tau and p‐tau181 in Alzheimer’s disease and rapidly progressive dementias. Alzheimers Dement. 2024 20 1 745 751 10.1002/alz.13516 37858957
    [Google Scholar]
  30. Hansen N Juhl A L Grenzer I M Cerebrospinal fluid total tau protein correlates with longitudinal, progressing cognitive dysfunction in anti-neural autoantibody-associated dementia and alzheimer's dementia: A case-control study Front Immunol. 2022 13 837376 10.3389/fimmu.2022.837376
    [Google Scholar]
  31. Hesse C. Rosengren L. Andreasen N. Davidsson P. Vanderstichele H. Vanmechelen E. Blennow K. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci. Lett. 2001 297 3 187 190 10.1016/S0304‑3940(00)01697‑9 11137759
    [Google Scholar]
  32. Cicognola C. Brinkmalm G. Wahlgren J. Portelius E. Gobom J. Cullen N.C. Hansson O. Parnetti L. Constantinescu R. Wildsmith K. Chen H.H. Beach T.G. Lashley T. Zetterberg H. Blennow K. Höglund K. Novel tau fragments in cerebrospinal fluid: Relation to tangle pathology and cognitive decline in Alzheimer’s disease. Acta Neuropathol. 2019 137 2 279 296 10.1007/s00401‑018‑1948‑2 30547227
    [Google Scholar]
  33. Hall S. Öhrfelt A. Constantinescu R. Andreasson U. Surova Y. Bostrom F. Nilsson C. Widner H. Decraemer H. Nägga K. Minthon L. Londos E. Vanmechelen E. Holmberg B. Zetterberg H. Blennow K. Hansson O. Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders. Arch. Neurol. 2012 69 11 1445 1452 10.1001/archneurol.2012.1654 22925882
    [Google Scholar]
  34. Urakami K. Wada K. Arai H. Sasaki H. Kanai M. Shoji M. Ishizu H. Kashihara K. Yamamoto M. Tsuchiya-Ikemoto K. Morimatsu M. Takashima H. Nakagawa M. Kurokawa K. Maruyama H. Kaseda Y. Nakamura S. Hasegawa K. Oono H. Hikasa C. Ikeda K. Yamagata K. Wakutani Y. Takeshima T. Nakashima K. Diagnostic significance of tau protein in cerebrospinal fluid from patients with corticobasal degeneration or progressive supranuclear palsy. J. Neurol. Sci. 2001 183 1 95 98 10.1016/S0022‑510X(00)00480‑9 11166802
    [Google Scholar]
  35. Iqbal K. Alonso A.C. Chen S. Chohan M.O. El-Akkad E. Gong C.X. Khatoon S. Li B. Liu F. Rahman A. Tanimukai H. Grundke-Iqbal I. Tau pathology in Alzheimer disease and other tauopathies. Biochim. Biophys. Acta 2005 1739 2-3 198 210 10.1016/j.bbadis.2004.09.008 15615638
    [Google Scholar]
  36. Chong J.R. Ashton N.J. Karikari T.K. Tanaka T. Schöll M. Zetterberg H. Blennow K. Chen C.P. Lai M.K.P. Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer’s disease: A focused review on recent advances. J. Neurol. Neurosurg. Psychiatry 2021 92 11 1231 1241 10.1136/jnnp‑2021‑327370 34510001
    [Google Scholar]
  37. Janelidze S. Mattsson N. Palmqvist S. Smith R. Beach T.G. Serrano G.E. Chai X. Proctor N.K. Eichenlaub U. Zetterberg H. Blennow K. Reiman E.M. Stomrud E. Dage J.L. Hansson O. Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia. Nat. Med. 2020 26 3 379 386 10.1038/s41591‑020‑0755‑1 32123385
    [Google Scholar]
  38. Karikari T.K. Pascoal T.A. Ashton N.J. Janelidze S. Benedet A.L. Rodriguez J.L. Chamoun M. Savard M. Kang M.S. Therriault J. Schöll M. Massarweh G. Soucy J.P. Höglund K. Brinkmalm G. Mattsson N. Palmqvist S. Gauthier S. Stomrud E. Zetterberg H. Hansson O. Rosa-Neto P. Blennow K. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: A diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020 19 5 422 433 10.1016/S1474‑4422(20)30071‑5 32333900
    [Google Scholar]
  39. Janelidze S. Stomrud E. Smith R. Palmqvist S. Mattsson N. Airey D.C. Proctor N.K. Chai X. Shcherbinin S. Sims J.R. Triana-Baltzer G. Theunis C. Slemmon R. Mercken M. Kolb H. Dage J.L. Hansson O. Cerebrospinal fluid p-tau217 performs better than p-tau181 as a biomarker of Alzheimer’s disease. Nat. Commun. 2020 11 1 1683 10.1038/s41467‑020‑15436‑0 32246036
    [Google Scholar]
  40. Palmqvist S. Janelidze S. Quiroz Y.T. Zetterberg H. Lopera F. Stomrud E. Su Y. Chen Y. Serrano G.E. Leuzy A. Mattsson-Carlgren N. Strandberg O. Smith R. Villegas A. Sepulveda-Falla D. Chai X. Proctor N.K. Beach T.G. Blennow K. Dage J.L. Reiman E.M. Hansson O. Discriminative accuracy of plasma phospho-tau217 for alzheimer disease vs other neurodegenerative disorders. JAMA 2020 324 8 772 781 10.1001/jama.2020.12134 32722745
    [Google Scholar]
  41. Wennström M. Janelidze S. Nilsson K.P.R. Serrano G.E. Beach T.G. Dage J.L. Hansson O. Cellular localization of p-tau217 in brain and its association with p-tau217 plasma levels. Acta Neuropathol. Commun. 2022 10 1 3 10.1186/s40478‑021‑01307‑2 34991721
    [Google Scholar]
  42. Huang S. Wang Y.J. Guo J. Biofluid biomarkers of alzheimer’s disease: Progress, problems, and perspectives. Neurosci. Bull. 2022 38 6 677 691 10.1007/s12264‑022‑00836‑7 35306613
    [Google Scholar]
  43. Thijssen E.H. La Joie R. Strom A. Fonseca C. Iaccarino L. Wolf A. Spina S. Allen I.E. Cobigo Y. Heuer H. VandeVrede L. Proctor N.K. Lago A.L. Baker S. Sivasankaran R. Kieloch A. Kinhikar A. Yu L. Valentin M.A. Jeromin A. Zetterberg H. Hansson O. Mattsson-Carlgren N. Graham D. Blennow K. Kramer J.H. Grinberg L.T. Seeley W.W. Rosen H. Boeve B.F. Miller B.L. Teunissen C.E. Rabinovici G.D. Rojas J.C. Dage J.L. Boxer A.L. Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer’s disease and frontotemporal lobar degeneration: A retrospective diagnostic performance study. Lancet Neurol. 2021 20 9 739 752 10.1016/S1474‑4422(21)00214‑3 34418401
    [Google Scholar]
  44. Janelidze S. Berron D. Smith R. Strandberg O. Proctor N.K. Dage J.L. Stomrud E. Palmqvist S. Mattsson-Carlgren N. Hansson O. Associations of plasma phospho-tau217 levels with tau positron emission tomography in early alzheimer disease. JAMA Neurol. 2021 78 2 149 156 10.1001/jamaneurol.2020.4201 33165506
    [Google Scholar]
  45. Brickman A.M. Manly J.J. Honig L.S. Sanchez D. Reyes-Dumeyer D. Lantigua R.A. Lao P.J. Stern Y. Vonsattel J.P. Teich A.F. Airey D.C. Proctor N.K. Dage J.L. Mayeux R. Plasma p‐tau181, p‐tau217, and other blood‐based Alzheimer’s disease biomarkers in a multi‐ethnic, community study. Alzheimers Dement. 2021 17 8 1353 1364 10.1002/alz.12301 33580742
    [Google Scholar]
  46. Biswas A. Mukherjee A. CSF P-tau 231 as biomarker in alzheimer’s disease. Ann. Indian Acad. Neurol. 2022 25 6 36911494
    [Google Scholar]
  47. Michno W. Nyström S. Wehrli P. Lashley T. Brinkmalm G. Guerard L. Syvänen S. Sehlin D. Kaya I. Brinet D. Nilsson K.P.R. Hammarström P. Blennow K. Zetterberg H. Hanrieder J. Pyroglutamation of amyloid-βx-42 (Aβx-42) followed by Aβ1–40 deposition underlies plaque polymorphism in progressing Alzheimer’s disease pathology. J. Biol. Chem. 2019 294 17 6719 6732 10.1074/jbc.RA118.006604 30814252
    [Google Scholar]
  48. Seubert P. Vigo-Pelfrey C. Esch F. Lee M. Dovey H. Davis D. Sinha S. Schiossmacher M. Whaley J. Swindlehurst C. McCormack R. Wolfert R. Selkoe D. Lieberburg I. Schenk D. Isolation and quantification of soluble Alzheimer’s β-peptide from biological fluids. Nature 1992 359 6393 325 327 10.1038/359325a0 1406936
    [Google Scholar]
  49. Orobets K.S. Karamyshev A.L. Amyloid precursor protein and alzheimer’s disease. Int. J. Mol. Sci. 2023 24 19 14794 10.3390/ijms241914794 37834241
    [Google Scholar]
  50. Cai W. Li L. Sang S. Pan X. Zhong C. Physiological roles of β-amyloid in regulating synaptic function: Implications for ad pathophysiology. Neurosci. Bull. 2023 39 8 1289 1308 10.1007/s12264‑022‑00985‑9 36443453
    [Google Scholar]
  51. Hu X. Leak R.K. Shi Y. Suenaga J. Gao Y. Zheng P. Chen J. Microglial and macrophage polarization—new prospects for brain repair. Nat. Rev. Neurol. 2015 11 1 56 64 10.1038/nrneurol.2014.207 25385337
    [Google Scholar]
  52. Merighi S. Nigro M. Travagli A. Gessi S. Microglia and alzheimer’s disease. Int. J. Mol. Sci. 2022 23 21 12990 10.3390/ijms232112990 36361780
    [Google Scholar]
  53. Hang-Juan W. Li L. Xin L. Imperatorin alleviates Aβ-induced spatial learning memory impairment and neuroinflammation in model mice of Alzheimer disease. Zhongguo Yaolixue Yu Dulixue Zazhi 2021 35 09 642 643
    [Google Scholar]
  54. Andreasen N. Hesse C. Davidsson P. Minthon L. Wallin A. Winblad B. Vanderstichele H. Vanmechelen E. Blennow K. Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: Differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch. Neurol. 1999 56 6 673 680 10.1001/archneur.56.6.673 10369305
    [Google Scholar]
  55. Jarrett J.T. Berger E.P. Lansbury P.T. Jr The C-terminus of the beta protein is critical in amyloidogenesis. Ann. N. Y. Acad. Sci. 1993 695 1 144 148 10.1111/j.1749‑6632.1993.tb23043.x 8239273
    [Google Scholar]
  56. Kuo Y.M. Emmerling M.R. Vigo-Pelfrey C. Kasunic T.C. Kirkpatrick J.B. Murdoch G.H. Ball M.J. Roher A.E. Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. J. Biol. Chem. 1996 271 8 4077 4081 10.1074/jbc.271.8.4077 8626743
    [Google Scholar]
  57. Sturchio A. Dwivedi A.K. Young C.B. Malm T. Marsili L. Sharma J.S. Mahajan A. Hill E.J. Andaloussi S.E.L. Poston K.L. Manfredsson F.P. Schneider L.S. Ezzat K. Espay A.J. High cerebrospinal amyloid-β 42 is associated with normal cognition in individuals with brain amyloidosis. EClinicalMedicine 2021 38 100988 10.1016/j.eclinm.2021.100988 34505023
    [Google Scholar]
  58. Janelidze S. Stomrud E. Palmqvist S. Zetterberg H. van Westen D. Jeromin A. Song L. Hanlon D. Tan Hehir C.A. Baker D. Blennow K. Hansson O. Plasma β-amyloid in Alzheimer’s disease and vascular disease. Sci. Rep. 2016 6 1 26801 10.1038/srep26801 27241045
    [Google Scholar]
  59. Gu L. Guo Z. Alzheimer’s Aβ42 and Aβ40 peptides form interlaced amyloid fibrils. J. Neurochem. 2013 126 3 305 311 10.1111/jnc.12202 23406382
    [Google Scholar]
  60. Jiannan L Qiang M Study on the correlation between peripheral blood markers Aβ42,Aβ40,P-tau protein and Hcy in patients with Alzheimer’s disease. J. Neurochem. 2022 44 07 965 969+975
    [Google Scholar]
  61. Hsu J.L. Lee W.J. Liao Y.C. Lirng J.F. Wang S.J. Fuh J.L. Plasma biomarkers are associated with agitation and regional brain atrophy in Alzheimer’s disease. Sci. Rep. 2017 7 1 5035 10.1038/s41598‑017‑05390‑1 28698646
    [Google Scholar]
  62. Palmqvist S. Zetterberg H. Mattsson N. Johansson P. Minthon L. Blennow K. Olsson M. Hansson O. Hansson O. Minthon L. Toresson H. Nägga K. Palmqvist S. Stomrud E. Johansson P. Nilsson C. Nilsson M. Mattsson N. Lindqvist D. Vestberg S. Janelidze S. Zetterberg H. Blennow K. Andreasson U. van Westen D. Lätt J. Mannfolk P. Nilsson M. Strandberg O. Sundgren P. Ståhlberg F. Lindberg O. Westman E. Wahlund L-O. Wollmer P. Smith R. Olsson T. Weiner M. Aisen P. Weiner M. Aisen P. Petersen R. Jack C.R. Jr Jagust W. Trojanowki J.Q. Toga A.W. Beckett L. Green R.C. Gamst A. Saykin A.J. Morris J. Potter W.Z. Green R.C. Montine T. Petersen R. Aisen P. Gamst A. Thomas R.G. Donohue M. Walter S. Jack C.R. Jr Dale A. Bernstein M. Felmlee J. Fox N. Thompson P. Schuff N. Alexander G. DeCarli C. Jagust W. Bandy D. Koeppe R.A. Foster N. Reiman E.M. Chen K. Mathis C. Morris J. Cairns N.J. Taylor-Reinwald L. Trojanowki J.Q. Shaw L. Lee V.M-Y. Korecka M. Toga A.W. Crawford K. Neu S. Beckett L. Harvey D. Gamst A. Kornak J. Saykin A.J. Foroud T.M. Potkin S. Shen L. Kachaturian Z. Frank R. Snyder P.J. Molchan S. Kaye J. Dolen S. Quinn J. Schneider L. Pawluczyk S. Spann B.M. Brewer J. Vanderswag H. Heidebrink J.L. Lord J.L. Petersen R. Johnson K. Doody R.S. Villanueva-Meyer J. Chowdhury M. Stern Y. Honig L.S. Bell K.L. Morris J.C. Mintun M.A. Schneider S. Marson D. Griffith R. Clark D. Grossman H. Tang C. Marzloff G. deToledo-Morrell L. Shah R.C. Duara R. Varon D. Roberts CAN P. Albert M.S. Kozauer N. Zerrate M. Rusinek H. de Leon M.J. De Santi S.M. Doraiswamy P.M. Petrella J.R. Aiello M. Arnold S. Karlawish J.H. Wolk D. Smith C.D. Given C.A. II Hardy P. Lopez O.L. Oakley M.A. Simpson D.M. Ismail M.S. Brand C. Richard J. Mulnard R.A. Thai G. Mc-Adams-Ortiz C. Diaz-Arrastia R. Martin-Cook K. DeVous M. Levey A.I. Lah J.J. Cellar J.S. Burns J.M. Anderson H.S. Laubinger M.M. Apostolova L. Silverman D.H.S. Lu P.H. Graff-Radford N.R. Parfitt F. Johnson H. Farlow M. Herring S. Hake A.M. van Dyck C.H. MacAvoy M.G. Benincasa A.L. Chertkow H. Bergman H. Hosein C. Black S. Stefanovic B. Caldwell C. Robin Hsiung G-Y. Feldman H. Assaly M. Kertesz A. Rogers J. Trost D. Bernick C. Munic D. Wu C-K. Johnson N. Mesulam M. Sadowsky C. Martinez W. Villena T. Turner R.S. Johnson K. Reynolds B. Sperling R.A. Rentz D.M. Johnson K.A. Rosen A. Tinklenberg J. Ashford W. Sabbagh M. Connor D. Jacobson S. Killiany R. Norbash A. Nair A. Obisesan T.O. Jayam-Trouth A. Wang P. Lerner A. Hudson L. Ogrocki P. DeCarli C. Fletcher E. Carmichael O. Kittur S. Borrie M. Lee T-Y. Bartha R. Johnson S. Asthana S. Carlsson C.M. Potkin S.G. Preda A. Nguyen D. Tariot P. Fleisher A. Reeder S. Bates V. Capote H. Rainka M. Hendin B.A. Scharre D.W. Kataki M. Zimmerman E.A. Celmins D. Brown A.D. Pearlson G. Blank K. Anderson K. Saykin A.J. Santulli R.B. Englert J. Williamson J.D. Sink K.M. Watkins F. Ott B.R. Stopa E. Tremont G. Salloway S. Malloy P. Correia S. Rosen H.J. Mintzer J. Longmire C.F. Spicer K. Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology 2015 85 14 1240 1249 10.1212/WNL.0000000000001991 26354982
    [Google Scholar]
  63. Ovod V. Ramsey K.N. Mawuenyega K.G. Bollinger J.G. Hicks T. Schneider T. Sullivan M. Paumier K. Holtzman D.M. Morris J.C. Benzinger T. Fagan A.M. Patterson B.W. Bateman R.J. Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement. 2017 13 8 841 849 10.1016/j.jalz.2017.06.2266 28734653
    [Google Scholar]
  64. Wiltfang J. Esselmann H. Bibl M. Hüll M. Hampel H. Kessler H. Frölich L. Schröder J. Peters O. Jessen F. Luckhaus C. Perneczky R. Jahn H. Fiszer M. Maler J.M. Zimmermann R. Bruckmoser R. Kornhuber J. Lewczuk P. Amyloid β peptide ratio 42/40 but not Aβ42 correlates with phospho‐Tau in patients with low‐ and high‐CSF Aβ40 load. J. Neurochem. 2007 101 4 1053 1059 10.1111/j.1471‑4159.2006.04404.x 17254013
    [Google Scholar]
  65. Stevenson-Hoare J. Heslegrave A. Leonenko G. Fathalla D. Bellou E. Luckcuck L. Marshall R. Sims R. Morgan B.P. Hardy J. de Strooper B. Williams J. Zetterberg H. Escott-Price V. Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer’s disease. Brain 2023 146 2 690 699 10.1093/brain/awac128 35383826
    [Google Scholar]
  66. Nakamura A. Kaneko N. Villemagne V.L. Kato T. Doecke J. Doré V. Fowler C. Li Q.X. Martins R. Rowe C. Tomita T. Matsuzaki K. Ishii K. Ishii K. Arahata Y. Iwamoto S. Ito K. Tanaka K. Masters C.L. Yanagisawa K. High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature 2018 554 7691 249 254 10.1038/nature25456 29420472
    [Google Scholar]
  67. Fagan A.M. Shaw L.M. Xiong C. Vanderstichele H. Mintun M.A. Trojanowski J.Q. Coart E. Morris J.C. Holtzman D.M. Comparison of analytical platforms for cerebrospinal fluid measures of β-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch. Neurol. 2011 68 9 1137 1144 10.1001/archneurol.2011.105 21555603
    [Google Scholar]
  68. Li Q.X. Villemagne V.L. Doecke J.D. Rembach A. Sarros S. Varghese S. McGlade A. Laughton K.M. Pertile K.K. Fowler C.J. Rumble R.L. Trounson B.O. Taddei K. Rainey-Smith S.R. Laws S.M. Robertson J.S. Evered L.A. Silbert B. Ellis K.A. Rowe C.C. Macaulay S.L. Darby D. Martins R.N. Ames D. Masters C.L. Collins S. Alzheimer’s disease normative cerebrospinal fluid biomarkers validated in PET Amyloid-β characterized subjects from the australian imaging, biomarkers and lifestyle (AIBL) study. J. Alzheimers Dis. 2015 48 1 175 187 10.3233/JAD‑150247 26401938
    [Google Scholar]
  69. Quan C. Yong P. Research advances in the imaging findings of Alzheimer’s disease. J. Int. Neurol. Neurosurg. 2022 49 05 60 66
    [Google Scholar]
  70. Yu Q. Mai Y. Ruan Y. Luo Y. Zhao L. Fang W. Cao Z. Li Y. Liao W. Xiao S. Mok V.C.T. Shi L. Liu J. An MRI-based strategy for differentiation of frontotemporal dementia and Alzheimer’s disease. Alzheimers Res. Ther. 2021 13 1 23 10.1186/s13195‑020‑00757‑5 33436059
    [Google Scholar]
  71. Dash S. Agarwal Y. Jain S. Sharma A. Chaudhry N. Perfusion CT imaging as a diagnostic and prognostic tool for dementia: Prospective case-control study. Postgrad. Med. J. 2022 postgradmedj-2021-141264 37076646
    [Google Scholar]
  72. Valotassiou V. Malamitsi J. Papatriantafyllou J. Dardiotis E. Tsougos I. Psimadas D. Alexiou S. Hadjigeorgiou G. Georgoulias P. SPECT and PET imaging in Alzheimer’s disease. Ann. Nucl. Med. 2018 32 9 583 593 10.1007/s12149‑018‑1292‑6 30128693
    [Google Scholar]
  73. Valotassiou V. Wozniak G. Sifakis N. Demakopoulos N. Georgoulias P. Radiopharmaceuticals in neurological and psychiatric disorders. Curr. Clin. Pharmacol. 2008 3 2 99 107 10.2174/157488408784293679 18690884
    [Google Scholar]
  74. Klunk W.E. Engler H. Nordberg A. Wang Y. Blomqvist G. Holt D.P. Bergström M. Savitcheva I. Huang G.F. Estrada S. Ausén B. Debnath M.L. Barletta J. Price J.C. Sandell J. Lopresti B.J. Wall A. Koivisto P. Antoni G. Mathis C.A. Långström B. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound‐B. Ann. Neurol. 2004 55 3 306 319 10.1002/ana.20009 14991808
    [Google Scholar]
  75. Chu L.W. Alzheimer’s disease: Early diagnosis and treatment. Hong Kong Med. J. 2012 18 3 228 237 22665688
    [Google Scholar]
  76. Cho H. Seo S.W. Kim J.H. Suh M.K. Lee J.H. Choe Y.S. Lee K.H. Kim J.S. Kim G.H. Noh Y. Ye B.S. Kim H.J. Yoon C.W. Chin J. Na D.L. Amyloid deposition in early onset versus late onset Alzheimer’s disease. J. Alzheimers Dis. 2013 35 4 813 821 10.3233/JAD‑121927 23507771
    [Google Scholar]
  77. Rabinovici G.D. Furst A.J. O’Neil J.P. Racine C.A. Mormino E.C. Baker S.L. Chetty S. Patel P. Pagliaro T.A. Klunk W.E. Mathis C.A. Rosen H.J. Miller B.L. Jagust W.J. 11 C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology 2007 68 15 1205 1212 10.1212/01.wnl.0000259035.98480.ed 17420404
    [Google Scholar]
  78. Ma Y. Zhang S. Li J. Zheng D.M. Guo Y. Feng J. Ren W.D. Predictive accuracy of amyloid imaging for progression from mild cognitive impairment to Alzheimer disease with different lengths of follow-up: A meta-analysis. [Corrected]. Medicine (Baltimore) 2014 93 27 e150 10.1097/MD.0000000000000150 25501055
    [Google Scholar]
  79. Villemagne V.L. Doré V. Burnham S.C. Masters C.L. Rowe C.C. Imaging tau and amyloid-β proteinopathies in Alzheimer disease and other conditions. Nat. Rev. Neurol. 2018 14 4 225 236 10.1038/nrneurol.2018.9 29449700
    [Google Scholar]
  80. Klunk W.E. Mathis C.A. Price J.C. Lopresti B.J. DeKosky S.T. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain 2006 129 11 2805 2807 10.1093/brain/awl281 17071918
    [Google Scholar]
  81. Kimura Y. Ichise M. Ito H. Shimada H. Ikoma Y. Seki C. Takano H. Kitamura S. Shinotoh H. Kawamura K. Zhang M.R. Sahara N. Suhara T. Higuchi M. PET quantification of tau pathology in human brain with 11 C-PBB3. J. Nucl. Med. 2015 56 9 1359 1365 10.2967/jnumed.115.160127 26182966
    [Google Scholar]
  82. Chiotis K. Dodich A. Boccardi M. Festari C. Drzezga A. Hansson O. Ossenkoppele R. Frisoni G. Garibotto V. Nordberg A. Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework. Eur. J. Nucl. Med. Mol. Imaging 2021 48 7 2086 2096 10.1007/s00259‑021‑05277‑4 33723628
    [Google Scholar]
  83. Ossenkoppele R. van der Kant R. Hansson O. Tau biomarkers in Alzheimer’s disease: towards implementation in clinical practice and trials. Lancet Neurol. 2022 21 8 726 734 10.1016/S1474‑4422(22)00168‑5 35643092
    [Google Scholar]
  84. Pontecorvo M.J. Devous M.D. Kennedy I. Navitsky M. Lu M. Galante N. Salloway S. Doraiswamy P.M. Southekal S. Arora A.K. McGeehan A. Lim N.C. Xiong H. Truocchio S.P. Joshi A.D. Shcherbinin S. Teske B. Fleisher A.S. Mintun M.A. A multicentre longitudinal study of flortaucipir (18F) in normal ageing, mild cognitive impairment and Alzheimer’s disease dementia. Brain 2019 142 6 1723 1735 10.1093/brain/awz090 31009046
    [Google Scholar]
  85. La Joie R. Visani A.V. Baker S.L. Brown J.A. Bourakova V. Cha J. Chaudhary K. Edwards L. Iaccarino L. Janabi M. Lesman-Segev O.H. Miller Z.A. Perry D.C. O’Neil J.P. Pham J. Rojas J.C. Rosen H.J. Seeley W.W. Tsai R.M. Miller B.L. Jagust W.J. Rabinovici G.D. Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET. Sci. Transl. Med. 2020 12 524 eaau5732 10.1126/scitranslmed.aau5732 31894103
    [Google Scholar]
  86. Groot C. Villeneuve S. Smith R. Hansson O. Ossenkoppele R. Tau PET imaging in neurodegenerative disorders. J. Nucl. Med. 2022 63 Suppl. 1 20S 26S 10.2967/jnumed.121.263196 35649647
    [Google Scholar]
  87. Leuzy A. Pascoal T.A. Strandberg O. Insel P. Smith R. Mattsson-Carlgren N. Benedet A.L. Cho H. Lyoo C.H. La Joie R. Rabinovici G.D. Ossenkoppele R. Rosa-Neto P. Hansson O. A multicenter comparison of [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis. Eur. J. Nucl. Med. Mol. Imaging 2021 48 7 2295 2305 10.1007/s00259‑021‑05401‑4 34041562
    [Google Scholar]
  88. Pluta R. Ułamek-Kozioł M. Lymphocytes, platelets, erythrocytes, and exosomes as possible biomarkers for alzheimer’s disease clinical diagnosis. Adv. Exp. Med. Biol. 2019 1118 71 82 10.1007/978‑3‑030‑05542‑4_4 30747418
    [Google Scholar]
  89. Canobbio I. Abubaker A.A. Visconte C. Torti M. Pula G. Role of amyloid peptides in vascular dysfunction and platelet dysregulation in Alzheimer’s disease. Front. Cell. Neurosci. 2015 9 65 10.3389/fncel.2015.00065 25784858
    [Google Scholar]
  90. Heneka M.T. Carson M.J. Khoury J.E. Landreth G.E. Brosseron F. Feinstein D.L. Jacobs A.H. Wyss-Coray T. Vitorica J. Ransohoff R.M. Herrup K. Frautschy S.A. Finsen B. Brown G.C. Verkhratsky A. Yamanaka K. Koistinaho J. Latz E. Halle A. Petzold G.C. Town T. Morgan D. Shinohara M.L. Perry V.H. Holmes C. Bazan N.G. Brooks D.J. Hunot S. Joseph B. Deigendesch N. Garaschuk O. Boddeke E. Dinarello C.A. Breitner J.C. Cole G.M. Golenbock D.T. Kummer M.P. Neuroinflammation in alzheimer’s disease. Lancet Neurol. 2015 14 4 388 405 10.1016/S1474‑4422(15)70016‑5 25792098
    [Google Scholar]
  91. Mietelska-Porowska A. Wojda U. T lymphocytes and inflammatory mediators in the interplay between brain and blood in alzheimer’s disease: potential pools of new biomarkers. J. Immunol. Res. 2017 2017 1 17 10.1155/2017/4626540 28293644
    [Google Scholar]
  92. Kiko T. Nakagawa K. Satoh A. Tsuduki T. Furukawa K. Arai H. Miyazawa T. Amyloid β levels in human red blood cells. PLoS One 2012 7 11 e49620 10.1371/journal.pone.0049620 23166730
    [Google Scholar]
  93. Stevenson A. Lopez D. Khoo P. Kalaria R.N. Mukaetova-Ladinska E.B. Exploring erythrocytes as blood biomarkers for alzheimer’s disease. J. Alzheimers Dis. 2017 60 3 845 857 10.3233/JAD‑170363 28984593
    [Google Scholar]
  94. Zhuang X. Xiang X. Grizzle W. Sun D. Zhang S. Axtell R.C. Ju S. Mu J. Zhang L. Steinman L. Miller D. Zhang H.G. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol. Ther. 2011 19 10 1769 1779 10.1038/mt.2011.164 21915101
    [Google Scholar]
  95. Pulliam L. Sun B. Mustapic M. Chawla S. Kapogiannis D. Plasma neuronal exosomes serve as biomarkers of cognitive impairment in HIV infection and Alzheimer’s disease. J. Neurovirol. 2019 25 5 702 709 10.1007/s13365‑018‑0695‑4 30610738
    [Google Scholar]
  96. Gawaz M. Langer H. May A.E. Platelets in inflammation and atherogenesis. J. Clin. Invest. 2005 115 12 3378 3384 10.1172/JCI27196 16322783
    [Google Scholar]
  97. Thal D.R. Griffin W.S.T. de Vos R.A.I. Ghebremedhin E. Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease. Acta Neuropathol. 2008 115 6 599 609 10.1007/s00401‑008‑0366‑2 18369648
    [Google Scholar]
  98. Catricala S. Torti M. Ricevuti G. Alzheimer disease and platelets: how’s that relevant. Immun. Ageing 2012 9 1 20 10.1186/1742‑4933‑9‑20 22985434
    [Google Scholar]
  99. Gowert N.S. Donner L. Chatterjee M. Eisele Y.S. Towhid S.T. Münzer P. Walker B. Ogorek I. Borst O. Grandoch M. Schaller M. Fischer J.W. Gawaz M. Weggen S. Lang F. Jucker M. Elvers M. Blood platelets in the progression of Alzheimer’s disease. PLoS One 2014 9 2 e90523 10.1371/journal.pone.0090523 24587388
    [Google Scholar]
  100. Prodan C.I. Szasz R. Vincent A.S. Ross E.D. Dale G.L. Coated-platelets retain amyloid precursor protein on their surface. Platelets 2006 17 1 56 60 10.1080/09537100500181913 16308188
    [Google Scholar]
  101. Prodan C.I. Ross E.D. Vincent A.S. Dale G.L. Rate of progression in Alzheimer’s disease correlates with coated-platelet levels—a longitudinal study. Transl. Res. 2008 152 3 99 102 10.1016/j.trsl.2008.07.001 18774538
    [Google Scholar]
  102. Pluta R. Ułamek-Kozioł M. Januszewski S. Czuczwar S.J. Platelets, lymphocytes and erythrocytes from Alzheimer’s disease patients: The quest for blood cell-based biomarkers. Folia Neuropathol. 2018 56 1 14 20 10.5114/fn.2018.74655 29663736
    [Google Scholar]
  103. Mota S.I. Costa R.O. Ferreira I.L. Santana I. Caldeira G.L. Padovano C. Fonseca A.C. Baldeiras I. Cunha C. Letra L. Oliveira C.R. Pereira C.M.F. Rego A.C. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer’s disease. Biochim. Biophys. Acta Mol. Basis Dis. 2015 1852 7 1428 1441 10.1016/j.bbadis.2015.03.015 25857617
    [Google Scholar]
  104. Wojsiat J. Prandelli C. Laskowska-Kaszub K. Martín-Requero A. Wojda U. Oxidative stress and aberrant cell cycle in alzheimer’s disease lymphocytes: diagnostic prospects. J. Alzheimers Dis. 2015 46 2 329 350 10.3233/JAD‑141977 25737047
    [Google Scholar]
  105. Wojda U. Alzheimer’s disease lymphocytes: potential for biomarkers? Biomarkers Med. 2016 10 1 1 4 10.2217/bmm.15.79 26640978
    [Google Scholar]
  106. Lueg G. Gross C.C. Lohmann H. Johnen A. Kemmling A. Deppe M. Groger J. Minnerup J. Wiendl H. Meuth S.G. Duning T. Clinical relevance of specific T-cell activation in the blood and cerebrospinal fluid of patients with mild Alzheimer’s disease. Neurobiol. Aging 2015 36 1 81 89 10.1016/j.neurobiolaging.2014.08.008 25277040
    [Google Scholar]
  107. Martorana A. Bulati M. Buffa S. Pellicanò M. Caruso C. Candore G. Colonna-Romano G. Immunosenescence, inflammation and Alzheimer’s disease. Longev. Healthspan 2012 1 1 8 10.1186/2046‑2395‑1‑8 24764513
    [Google Scholar]
  108. Schwartz M. Deczkowska A. Neurological disease as a failure of brain–immune crosstalk: The multiple faces of neuroinflammation. Trends Immunol. 2016 37 10 668 679 10.1016/j.it.2016.08.001 27616557
    [Google Scholar]
  109. Zhang J. Kong Q. Zhang Z. Ge P. Ba D. He W. Telomere dysfunction of lymphocytes in patients with Alzheimer disease. Cogn. Behav. Neurol. 2003 16 3 170 176 10.1097/00146965‑200309000‑00004 14501538
    [Google Scholar]
  110. Nakagawa K. Kiko T. Kuriwada S. Miyazawa T. Kimura F. Miyazawa T. Amyloid β induces adhesion of erythrocytes to endothelial cells and affects endothelial viability and functionality. Biosci. Biotechnol. Biochem. 2011 75 10 2030 2033 10.1271/bbb.110318 21979080
    [Google Scholar]
  111. Wojsiat J. Laskowska-Kaszub K. Mietelska-Porowska A. Wojda U. Search for Alzheimer’s disease biomarkers in blood cells: Hypotheses-driven approach. Biomarkers Med. 2017 11 10 917 931 10.2217/bmm‑2017‑0041 28976776
    [Google Scholar]
  112. Frühbeis C. Fröhlich D. Kuo W.P. Krämer-Albers E.M. Extracellular vesicles as mediators of neuron-glia communication. Front. Cell. Neurosci. 2013 7 182 10.3389/fncel.2013.00182 24194697
    [Google Scholar]
  113. Frühbeis C. Fröhlich D. Kuo W.P. Amphornrat J. Thilemann S. Saab A.S. Kirchhoff F. Möbius W. Goebbels S. Nave K.A. Schneider A. Simons M. Klugmann M. Trotter J. Krämer-Albers E.M. Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol. 2013 11 7 e1001604 10.1371/journal.pbio.1001604 23874151
    [Google Scholar]
  114. Soares Martins T. Trindade D. Vaz M. Campelo I. Almeida M. Trigo G. da Cruz e Silva O.A.B. Henriques A.G. Diagnostic and therapeutic potential of exosomes in Alzheimer’s disease. J. Neurochem. 2021 156 2 162 181 10.1111/jnc.15112 32618370
    [Google Scholar]
  115. Colombo M. Raposo G. Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014 30 1 255 289 10.1146/annurev‑cellbio‑101512‑122326 25288114
    [Google Scholar]
  116. Welge V. Fiege O. Lewczuk P. Mollenhauer B. Esselmann H. Klafki H.W. Wolf S. Trenkwalder C. Otto M. Kornhuber J. Wiltfang J. Bibl M. Combined CSF tau, p-tau181 and amyloid-β 38/40/42 for diagnosing Alzheimer’s disease. J. Neural Transm. (Vienna) 2009 116 2 203 212 10.1007/s00702‑008‑0177‑6 19142572
    [Google Scholar]
  117. Jia L. Qiu Q. Zhang H. Chu L. Du Y. Zhang J. Zhou C. Liang F. Shi S. Wang S. Qin W. Wang Q. Li F. Wang Q. Li Y. Shen L. Wei Y. Jia J. Concordance between the assessment of Aβ42, T‐tau, and P‐T181‐tau in peripheral blood neuronal‐derived exosomes and cerebrospinal fluid. Alzheimers Dement. 2019 15 8 1071 1080 10.1016/j.jalz.2019.05.002 31422798
    [Google Scholar]
  118. Domingues C. da Cruz E Silva O.A.B. Henriques A.G. Impact of cytokines and chemokines on alzheimer’s disease neuropathological hallmarks. Curr. Alzheimer Res. 2017 14 8 870 882 28317487
    [Google Scholar]
  119. Goetzl E.J. Schwartz J.B. Abner E.L. Jicha G.A. Kapogiannis D. High complement levels in astrocyte‐derived exosomes of Alzheimer disease. Ann. Neurol. 2018 83 3 544 552 10.1002/ana.25172 29406582
    [Google Scholar]
  120. Goetzl E.J. Kapogiannis D. Schwartz J.B. Lobach I.V. Goetzl L. Abner E.L. Jicha G.A. Karydas A.M. Boxer A. Miller B.L. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer’s disease. FASEB J. 2016 30 12 4141 4148 10.1096/fj.201600816R 27601437
    [Google Scholar]
  121. Goetzl E.J. Abner E.L. Jicha G.A. Kapogiannis D. Schwartz J.B. Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer’s disease. FASEB J. 2018 32 2 888 893 10.1096/fj.201700731R 29025866
    [Google Scholar]
  122. Cheng L. Doecke J.D. Sharples R.A. Villemagne V.L. Fowler C.J. Rembach A. Martins R.N. Rowe C.C. Macaulay S.L. Masters C.L. Hill A.F. Prognostic serum miRNA biomarkers associated with Alzheimer’s disease shows concordance with neuropsychological and neuroimaging assessment. Mol. Psychiatry 2015 20 10 1188 1196 10.1038/mp.2014.127 25349172
    [Google Scholar]
/content/journals/car/10.2174/0115672050366767241223050957
Loading

  • Article Type:
    Review Article
Keywords: β-amyloid ; tau protein ; blood cells ; biomarkers ; Alzheimer's disease
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test